This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Dengue is a virus which is responsible for 100 million cases of dengue fever annually, and is one of the leading causes of death in children in several Asian countries. The virus has two principal mosquito vectors;Aedes ageypti and Aedes albopictus, which are responsible for transmitting disease to humans. Due to the global burden of illness associated with this disease, the development of an effective vaccine is imperative. On a global scale, the dengue virus causes a significant amount of illness and disability annually;a safe and effective vaccine is desperately needed. The aim of the current study is to determine the safety and effectiveness, in human volunteers, of a new lot of dengue virus vaccine. This study is a randomized, placebo-controlled, double-blind study in healthy volunteers. We will be conducting this study in conjunction with Johns Hopkins University in Baltimore, Maryland. Our colleagues at Johns Hopkins have already tested a different lot of this same vaccine and found it to be safe and well-tolerated in initial Phase II trials in human volunteers. (Durbin et al. Am J Trop Med. Hyg., 65(5),2001:405-413). This study is a randomized, placebo-controlled, double-blind study of healthy male and non-pregnant female volunteers 18-50 years of age with no history of a previous flavivirus infection. Eligibility for enrollment will be based on results of medical history, physical exam, liver and kidney testing, coagulation studies, HIV testing, hepatitis B and C screening, pregnancy testing, screening for previous flavivirus infection and hematology screening. Volunteers who fulfill inclusion and exclusion criteria will be recruited to participate. Volunteers in each treatment group will be randomly assigned to receive either the vaccine or placebo. The vaccine to placebo ratio will be 2.5:1 respectively. On dosing day, after review of the informed consent, each group will receive either vaccine or placebo via subcutaneous injection into their upper arm. The participants will be monitored after the vaccine by physicians and nurses at the GCRC. After a brief observation period they will be given diary cards and thermometers with instructions on how to use them. Volunteers will also receive contact information for the study doctor who will be available to them 24 hours a day 7 days a week for the duration of the study. Each volunteer will return to the GCRC on study days 2, 4, 6, 8, 10, 12, 14, 21, 28, 42 and 180 for a brief visit with the study physician and blood work. The purpose of the blood work is to monitor the level of viremia, immunologic indices in response to this viremia, and to follow kidney, liver and hematologic function in each volunteer. These visits will continue for the duration of the study.